Tumor-node response heterogeneity: Exploring the “spatial biology” of neoadjuvant therapy response in rectal cancer and its clinical implications

Figure 2 Spectrum of lymph node responses to neoadjuvant chemoradiotherapy and the biological significance of lymph node regression grade. Metastatic lymph nodes exhibit three primary patterns of response to neoadjuvant chemoradiotherapy: (1) Complete clearance lymph node regression grade (LRG1), characterized by fibrous scarring or acellular mucin lakes; (2) Partial regression (LRG2-5), with residual tumor cells embedded in a fibrotic stroma; and (3) Intrinsic resistance (LRG4-5), where tumor cells show almost no regression. The outcomes observed are the result of a combination of mechanisms, including immune clearance, treatment-induced senescence, fibrous encapsulation, and the selection of resistant clones by the immune microenvironment. lymph node regression grade, when utilised as a histological indicator, offers a direct reflection of the resistance capacity of the lymph node microenvironment. Its grade has been shown to be closely associated with patient prognosis. nCRT: Neoadjuvant chemoradiotherapy; LRG: Lymph node regression grade.